Evidence map›Paper›PMID 42039384›Full record

ArticlebioRxiv : the preprint server for biology2026

Multiomic screening platform uncovers the impact of histone mutations on chromatin and cell fate.

Ziyang Ye, Alireza Khademi, Renée L Barbosa, Foster Birnbaum, Margaret R Brown, Colin E Fowler, Arianna Arroyo-Ortega, Daniel Lee, Lijuan Feng, Leah A Gates and 4 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Ziyang YeKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA, 02139, USA.
Alireza KhademiKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA, 02139, USA.
Renée L BarbosaKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA, 02139, USA.
Foster BirnbaumDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Margaret R BrownKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA, 02139, USA.
Colin E FowlerKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA, 02139, USA.
Arianna Arroyo-OrtegaKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA, 02139, USA.
Daniel LeeKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA, 02139, USA.
Lijuan FengDepartments of Pathology & Immunology and Genetics, WashU Medicine, St. Louis, MO, 63110, USA.
Leah A GatesDepartment of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
Agata L PatriotisKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA, 02139, USA.ORCID 0000-0002-8237-975X
Amy E KeatingKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA, 02139, USA.ORCID 0000-0003-4074-8980
Francisco J Sánchez-RiveraKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA, 02139, USA.ORCID 0000-0002-8466-8563
Yadira M Soto-FelicianoKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA, 02139, USA.ORCID 0000-0001-5118-8478

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jacqueline A. Lees · 1985 to 2026
$93.9M
Mutant p53 in Tumorigenesis, Invasion, and MetastasisP01CA291694 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI James J Manfredi · 2025 to 2026
$7.9M
Understanding mechanisms of transcriptional regulation by chromatin adaptor proteinsR00GM140265 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SOTO-FELICIANO, YADIRA M · 2022 to 2024
$747k
Mechanisms of de novo Germline Histone Mutations Underlying Developmental DisordersR00HD107908 · NICHD · WASHINGTON UNIVERSITY · PI Lijuan Feng · 2025 to 2026
$496k
NCI NIH HHS P01 CA291694NCI NIH HHS P30 CA014051NICHD NIH HHS R00 HD107908NIGMS NIH HHS R00 GM140265
6 · The paper itself

Abstract

Somatic missense mutations in histone genes, often referred to as 'oncohistones', have been identified in diverse types of human cancers. The functional and mechanistic impact of most oncohistones remains unknown. To address this gap, we developed CHANCLA, a modular platform for high-throughput functional screening of oncohistones using multiomic phenotypic readouts. We used CHANCLA to systematically measure the impact of 303 human oncohistones on cellular proliferation, differentiation, histone-specific post-translational modifications, and chromatin accessibility. Integrative multiomic analyses revealed discrete oncohistone molecular classes that promote proliferation, block lineage-specific differentiation, and physically remodel the chromatin landscape by altering specific histone modifications and reducing nucleosome stability. Structural mapping and computational modeling studies uncovered that functionally convergent mutations are clustered at key nucleosome interfaces, particularly H2B-H4, and that chromatin accessibility-promoting mutations are linked to mono-nucleosome destabilization. Leveraging this multiomic resource, we discovered that the H3.3-Q5H mutant histone is a

Identifiers

PMID42039384
PMCPMC13104941

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.